Heparin-induced thrombocytopenia

Gowthami M Arepally, Gowthami M Arepally

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes to propagate a hypercoagulable state culminating in life-threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin exposure, but only a subset of sensitized patients progress to life-threatening complications of thrombocytopenia and thrombosis. Recent scientific developments have clarified mechanisms underlying PF4/heparin immunogenicity, disease susceptibility, and clinical manifestations of disease. Insights from clinical and laboratory findings have also been recently harnessed for disease prevention. This review will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and laboratory features, and management.

© 2017 by The American Society of Hematology.

Figures

Figure 1.
Figure 1.
A time line of key clinical and laboratory-based observations in HIT. Important clinical developments are provided above the time band, and major research observations are noted below. DTI, direct thrombin inhibitor; HITT, HIT with thrombosis; SRA, serotonin release assay.
Figure 2.
Figure 2.
Importance of PF4/heparin ultralarge complexes (ULCs) in HIT pathogenesis. (A) PF4, a positively charged protein, binds to negatively charged heparin through electrostatic interactions to form ULCs that govern HIT biology. At concentrations of PF4 or heparin excess, repulsive forces from excess charge predominate and are not permissive for complex formation. At stoichiometric ratios associated with charge neutralization, ULCs form capable of biological effects associated with in vivo immunogenicity (B), differential clinical effects of UFH and LMWH (C), and heparin-dependent reactivity in laboratory assays (D).

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Source: PubMed

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